Paternal Deprivation and Female Biparental Family Rearing Induce Dendritic and Synaptic Changes in Octodon degus: II. Nucleus Accumbens.

While the majority of studies on the importance of parental caregiving on offspring behavioral and brain development focus on the role of the mother, the paternal contribution is still an understudied topic. We investigated if growing up without paternal care affects dendritic and synaptic development in the nucleus accumbens of male and female offspring and if replacement of the father by a female caregiver "compensates" the impact of paternal deprivation. We compared (a) biparental rearing by father and mother, (b) monoparental care by a single mother, and (c) biparental rearing by two female caregivers. Quantitative analysis of medium-sized neurons in the nucleus accumbens revealed that growing up without father resulted in reduced spine number in both male and female offspring in the core region, whereas spine frequency was only reduced in females. In the shell region, reduced spine frequency was only found in males growing up in a monoparental environment. Replacement of the father by a female caregiver did not "protect" against the effects of paternal deprivation, indicating a critical impact of paternal care behavior on the development and maturation of neuronal networks in the nucleus accumbens.

Fostered offspring develop hyper-reactive endocrine stress responses in a plural-breeding rodent, Octodon degus.

Long-term parental separation can lead to altered behavioral and physical development in human children. Rodent models are popular for studying parent-child separation, and several studies have found that maternal separation leads to chronic changes in the endocrine stress response. However, while human children are generally raised by multiple caregivers, most rodent studies utilize solitary breeding species. Therefore, we used degus (Octodon degus) as a model for studying human parental separation, as these rodents practice plural breeding and communal care. In this study, we cross-fostered degu litters at different ages (post-natal day [PND] 2, 8, and 14) to test the hypotheses that fostering affects offspring stress hormone levels in both the short- and long-term and that these impacts differ depending on the age at which offspring are fostered. We found that fostering had long-term effects, as fostered offspring had higher stress-induced cortisol levels and weaker cortisol negative feedback than non-fostered offspring at weaning age (PND28). We also found that the timing of fostering mattered, as degus fostered at PND8 had higher baseline cortisol levels the day after fostering, while degus fostered at PND2 had higher stress-induced cortisol levels at weaning. These data suggest that long-term cross-fostering has enduring impacts on the endocrine stress response in degus, therefore making them a useful model organism for investigating impacts of parental separation in humans.

Chromatic pupillometry for the characterization of the pupillary light reflex in Octodon degus.

The common degu (Octodon degus) is an emerging model in biomedical science research due to its longevity and propensity to develop human-like conditions. However, there is a lack of standardized techniques for this non-traditional laboratory animal. In an effort to characterize the model, we developed a chromatic pupillometry setup and analysis protocol to characterize the pupillary light reflex (PLR) in our animals. The PLR is a biomarker to detect early signs for central nervous system deterioration. Chromatic pupillometry is a non-invasive and anesthesia-free method that can evaluate different aspects of the PLR, including the response of intrinsically photosensitive retinal ganglion cells (ipRGCs), the disfunction of which has been linked to various disorders. We studied the PLR of 12 degus between 6 and 48 months of age to characterize responses to LEDs of 390, 450, 500, 525 and 605 nm, and used 5 with overall better responses to establish a benchmark for healthy PLR (PLR+) and deteriorated PLR (PLR-). Degu pupils contracted up to 65% of their horizontal resting size before reaching saturation. The highest sensitivity was found at 500 nm, with similar sensitivities at lower tested intensities for 390 nm, coinciding with the medium wavelength and short wavelength cones of the degu. We also tested the post-illumination pupillary response (PIPR), which is driven exclusively by ipRGCs. PIPR was largest in response to 450 nm light, with the pupil preserving 48% of its maximum constriction 9 s after the stimulus, in contrast with 24% preserved in response to 525 nm, response driven mainly by cones. PLR- animals showed maximum constriction between 40% and 50% smaller than PLR+, and their PIPR almost disappeared, pointing to a disfunction of the iPRGCs rather than the retinal photoreceptors. Our method thus allows us to non-invasively estimate the condition of experimental animals before attempting other procedures.

Melatonin alleviates circadian system disruption induced by chronic shifts of the light-dark cycle in Octodon degus.

Modern 24-h society lifestyle is associated with experiencing frequent shifts in the lighting conditions which can negatively impact human health. Here, we use the degus, a species exhibiting diurnal and nocturnal chronotypes, to: (a) assess the impact of chronic shifts of the light:dark (LD) cycle in the animal's physiology and behaviour and (b) test the therapeutic potential of melatonin in enhancing rhythmicity under these conditions. Degus were subjected to a "5d + 2d" LD-shifting schedule for 19 weeks. This protocol aims to mimic lighting conditions experienced by humans during shift work: LD cycle was weekly delayed by 8h during 5 "working" days (Morning, Afternoon and Night schedule); during weekends (2 days), animals were kept under Morning schedule. After 9 weeks, melatonin was provided daily for 6h in the drinking water. The "5d + 2d" shifting LD schedule led to a disruption in wheel-running activity (WRA) and body temperature (Tb) rhythms which manifested up to three separate periods in the circadian range. This chronodisruption was more evident in nocturnal than in diurnal degus, particularly during the Afternoon schedule when a phase misalignment between WRA and Tb rhythms appeared. Melatonin treatment and, to a lesser extent, water restriction enhanced the 24-h component, suggesting a potential role in ameliorating the disruptive effects of shift work.

Stress, sleep, and sex: A review of endocrinological research in Octodon degus.

The Common Degu (Octodon degus) is a small rodent endemic to central Chile. It has become an important model for comparative vertebrate endocrinology because of several uncommon life-history features - it is diurnal, shows a high degree of sociality, practices plural breeding with multiple females sharing natal burrows, practices communal parental care, and can easily be studied in the laboratory and the field. Many studies have exploited these features to make contributions to comparative endocrinology. This review summarizes contributions in four major areas. First are studies on degu stress responses, focusing on seasonal changes in glucocorticoid (GC) release, impacts of parental care on offspring GC responses, and fitness consequences of individual variations of GC responses. These studies have helped confirm the ecological relevance of stress responses. Second are studies exploring diurnal circadian rhythms of melatonin and sex steroids. These studies have formed important work translating circadian biology from nocturnal laboratory rodents to diurnal humans. Third are studies that exploit the open nature of degu natural habitat, combined with laboratory studies, to explore the impact of testosterone on agonistic behavior. Studies have focused primarily on male:male, female:female, male:female, and parental behaviors. Fourth, are contributions to the study of female masculinization from male siblings in the uterus. These studies have focused on both the behavioral consequences of masculinization and the impact of those behaviors on fitness. Taken together, the studies reviewed here have formed a strong foundation for further studies in the degu so that future studies can address how endocrinological components underlie new mechanistic connections to the ecological effects on behavior and fitness.

Crouching to fit in: the energetic cost of locomotion in tunnels.

Animals that are specialized for a particular habitat or mode of locomotion often demonstrate locomotor efficiency in a focal environment when compared to a generalist species. However, measurements of these focal habitats or behaviors are often difficult or impossible to do in the field. In this study, the energetics and kinematics of simulated tunnel locomotion by two unrelated semi-fossorial mammals, the ferret and degu, were analyzed using open-flow respirometry and digital video. Animals were trained to move inside of normal (unconstrained, overground locomotion) and height-decreased (simulated tunnel, adjusted to tolerance limits for each species) Plexiglas chambers that were mounted flush onto a treadmill. Both absolute and relative tunnel performance differed between the species; ferrets tolerated a tunnel height that forced them to crouch at nearly 25% lower hip height than in an unconstrained condition, whereas degus would not perform on the treadmill past a ∼9% reduction in hip height. Both ferrets and degus exhibited significantly higher metabolic rates and cost of transport (CoT) values when moving in the tunnel condition relative to overground locomotion. When comparing CoT values across small (<10 kg) mammals, ferrets demonstrated a lower than predicted metabolic cost during both tunnel and terrestrial locomotion, whereas degus were very close to the line of best fit. Although tunnel locomotion requires a more striking change in posture for ferrets, ferrets are more efficient locomotors in both conditions than mammals of similar mass.

The modulating role of group stability on fitness effects of group size is different in females and males of a communally rearing rodent.

Group size may influence fitness benefits and costs that emerge from cooperative and competitive interactions in social species. However, evidence from plural breeding mammals indicates that group size is insufficient to explain variation in direct fitness, implying other attributes of social groups were overlooked. We studied the natural population of a social rodent during 5 years to test the hypothesis that social stability - in terms of group composition - modulates the effects of increasing number of breeding females (a proxy of communal rearing) and males on the number of offspring weaned (sired) and on the number of offspring weaned (sired) surviving to breeding age (two proxies of direct fitness). We quantified the effects of social stability (measured as changes in female or male group members between mating and the onset of lactation) on these fitness measures. We used live trapping, telemetry and DNA markers to determine social and fitness measures. Social stability in degus was variable in terms of the number of changes in group composition across groups. Low stability was mostly due to mortality and emigration of group members. Results supported a modulating role of social stability on the relationship between group size and the number of offspring weaned (sired). Stability in female and male group composition were both modulators of fitness to females and males. The modulatory role of stability was sex specific, where high social stability was often fitness beneficial to the females. Instead, low social stability was fitness enhancing to the males.

Masculinized females produce heavier offspring in a group living rodent.

Alternative morphotypes have been reported less frequently in females than in males. An exception to this rule is the gradient of phenotypical masculinization reported in some female mammals, in which feminized and masculinized females represent two opposite ends along this gradient. These phenotypical differences originate during prenatal development as the consequence of maternal effects. Feminized and masculinized females differ in several traits, including morphological, physiological, behavioural and reproductive traits. Differences previously reported in reproductive traits between feminized and masculinized females come mostly from mechanistic studies performed in the laboratory, and not necessarily on social species. As a result, it is unclear to what extent these reported differences between female alternative morphotypes materialize in wild, natural populations. We quantified the effect of female alternative morphotype on female reproductive traits in a natural population of Octodon degus, a highly social rodent. We assessed female alternative morphotype through a continuous gradient of anogenital distance. Thus, feminized females were close to the short end of anogenital distance, while masculinized females were close to the long end of this gradient. We also tested the hypothesis that the social environment interacts with female morphotype to influence female reproductive traits. In female degus, only body weight affected litter size, where heavier females weaned more offspring. Masculinized females delivered male-biased litters and weaned heavier offspring. Lastly, masculinized females gave birth later in the breeding season compared to feminized females. Contrary to previous claims, our findings do not support that masculinized females are less fertile than feminized females. Moreover, masculinized females produced heavier, potentially higher quality offspring compared with feminized females.

Effects of Habitat and Social Complexity on Brain Size, Brain Asymmetry and Dentate Gyrus Morphology in Two Octodontid Rodents.

Navigational and social challenges due to habitat conditions and sociality are known to influence dentate gyrus (DG) morphology, yet the relative importance of these factors remains unclear. Thus, we studied three natural populations of O. lunatus (Los Molles) and Octodon degus (El Salitre and Rinconada), two caviomorph species that differ in the extent of sociality and with contrasting vegetation cover of habitat used. The brains and DG of male and female breeding degus with simultaneous information on their physical and social environments were examined. The extent of sociality was quantified from total group size and range area overlap. O. degus at El Salitre was more social than at Rinconada and than O. lunatus from Los Molles. The use of transects to quantify cover of vegetation (and other physical objects in the habitat) and measures of the spatial behavior of animals indicated animal navigation based on unique cues or global landmarks is more cognitively challenging to O. lunatus. During lactation, female O. lunatus had larger brains than males. Relative DG volume was similar across sexes and populations. The right hemisphere of male and female O. lunatus had more cells than the left hemisphere, with DG directional asymmetry not found in O. degus. Degu population differences in brain size and DG cell number seemed more responsive to differences in habitat than to differences in sociality. Yet, large-sized O. degus (but not O. lunatus) that ranged over larger areas and were members of larger social groups had more DG cells per hemisphere. Thus, within-population variation in DG cell number by hemisphere was consistent with a joint influence of habitat and sociality in O. degus at El Salitre.

Maternal stress and plural breeding with communal care affect development of the endocrine stress response in a wild rodent.

Maternal stress can significantly affect offspring fitness. In laboratory rodents, chronically stressed mothers provide poor maternal care, resulting in pups with hyperactive stress responses. These hyperactive stress responses are characterized by high glucocorticoid levels in response to stressors plus poor negative feedback, which can ultimately lead to decreased fitness. In degus (Octodon degus) and other plural breeding rodents that exhibit communal care, however, maternal care from multiple females may buffer the negative impact on pups born to less parental mothers. We used wild, free-living degus to test this hypothesis. After parturition, we manipulated maternal stress by implanting cortisol pellets in 0%, 50-75%, or 100% of adult females within each social group. We then sampled pups for baseline and stress-induced cortisol, negative feedback efficacy, and adrenal sensitivity. From groups where all mothers were implanted with cortisol, pups had lower baseline cortisol levels and male pups additionally had weaker negative feedback compared to 0% or 50-75% implanted groups. Contrary to expectations, stress-induced cortisol did not differ between treatment groups. These data suggest that maternal stress impacts some aspects of the pup stress response, potentially through decreased maternal care, but that presence of unstressed mothers may mitigate some of these effects. Therefore, one benefit of plural breeding with communal care may be to buffer post-natal stress.

Postsynaptic dysfunction is associated with spatial and object recognition memory loss in a natural model of Alzheimer's disease.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder associated with progressive memory loss, severe dementia, and hallmark neuropathological markers, such as deposition of amyloid-ß (Aß) peptides in senile plaques and accumulation of hyperphosphorylated tau proteins in neurofibrillary tangles. Recent evidence obtained from transgenic mouse models suggests that soluble, nonfibrillar Aß oligomers may induce synaptic failure early in AD. Despite their undoubted value, these transgenic models rely on genetic manipulations that represent the inherited and familial, but not the most abundant, sporadic form of AD. A nontransgenic animal model that still develops hallmarks of AD would be an important step toward understanding how sporadic AD is initiated. Here we show that starting between 12 and 36 mo of age, the rodent Octodon degus naturally develops neuropathological signs of AD, such as accumulation of Aß oligomers and phosphorylated tau proteins. Moreover, age-related changes in Aß oligomers and tau phosphorylation levels are correlated with decreases in spatial and object recognition memory, postsynaptic function, and synaptic plasticity. These findings validate O. degus as a suitable natural model for studying how sporadic AD may be initiated.

Interplay between group size, huddling behavior and basal metabolism: an experimental approach in the social degu.

Mammals exposed to low temperatures increase their metabolic rate to maintain constant body temperature and thus compensate for heat loss. This high and costly energetic demand can be mitigated through thermoregulatory behavior such as social grouping or huddling, which helps to decrease metabolic rate as function of the numbers of individuals grouped. Sustained low temperatures in endothermic animals produce changes over time in rates of energy expenditure, by means of phenotypic plasticity. However, the putative modulating effect that huddling exerts on the flexibility of the basal metabolic rate (BMR) due to thermal acclimation remains unknown. We determined BMR values in Octodon degus, an endemic Chilean rodent, after being acclimated to either 15 or 30°C during 60 days, both alone and in groups of three and five individuals. At 15°C, BMR of huddling individuals was 40% lower than that of animals housed alone. Moreover, infrared thermography revealed a significant increase in local surface temperatures in huddled animals. Furthermore, individual thermal conductance was lower in individuals acclimated to 15°C than to 30°C, but no differences were observed between single and grouped animals. Our results indicate that huddling prevents an increase in BMR when animals are acclimated to cold conditions and that this effect is proportional to the number of animals grouped.

Seasonal variations of basal cortisol and high stress response to captivity in Octodon degus, a mammalian model species.

Across vertebrates, the hypothalamic-pituitary-adrenal axis is a conserved neuroendocrine network that responds to changing environments and involves the release of glucocorticoids into the blood. Few studies have been carried out concerning mammalian adrenal regulation in wild species either in the laboratory or field, and even fewer have been able to determine true glucocorticoid baselines. We studied the South-American caviomorph rodent Octodon degus, a diurnal and social mammal that has become an important species in the biological research. First, we determined the plasma cortisol baseline and the acute stress concentrations during the non-reproductive and mating seasons in free-living individuals. Second, using the same protocol we assessed the impact of long-term captivity on the adrenal function in wild-caught degus and degus born in laboratory. Third, we examined laboratory groups formed with degus taken from two distant natural populations; one of them originally occurs at the Andes Mountains in high altitude conditions. The data revealed seasonal modulation of basal cortisol in the wild associated with mating. In laboratory, degus presented higher cortisol stress responses, with greater magnitudes shown in degus born and reared in captivity. No differences between populations were found. The results suggest differential regulatory mechanisms between basal and stress-induced cortisol levels, and context dependence of cortisol modulation in a mammalian species.

Seasonal variation in the degu (Octodon degus) endocrine stress response.

Many wild animals show seasonal variation in circulating levels of stress hormones. Seasonal changes in the stress response may help animals better cope with the different challenges faced during each life history stage. We determined the seasonal stress profile of wild, free-living degus in Chile. Female degus were sampled during non-breeding (January), mating/early gestation (July), late gestation (August), and lactation (1st litter-September, 2nd litter-January). Male degus were sampled during the first three time-points. We measured baseline cortisol (CORT), stress-induced CORT, and negative feedback efficacy using a dexamethasone suppression test. While we found that neither males nor females showed seasonal variation in baseline CORT or negative feedback levels, we did find significant seasonal variation in stress-induced CORT levels of both sexes. Male stress-induced CORT was lowest during mating while female stress-induced CORT was highest during late gestation and lactation. Overall, females had higher stress-induced CORT compared to males. Our data suggest that stress-induced levels of CORT are highest during periods with increased chance of stressor exposure or times of positive energy balance. Consequently, CORT responses to stress appear to be regulated according to different life history needs.

Drinking preferences in chinchillas (Chinchilla laniger), degus (Octodon degu) and guinea pigs (Cavia porcellus).

Chinchilla (Chinchilla laniger), degus (Octodon degus) and guinea pigs (Cavia porcellus) are South American rodents living in a semi-arid habitat with varying, species-specific adaptations to water deprivation. Nonetheless, several diseases have been linked to insufficient water intake when these species are kept as pets, such as urolithiasis or obstipation. This study evaluated preferences for drinking systems. Six animals of each species were given a choice between an open dish and a nipple drinker. Food intake and water intake were measured daily for 13 days. Chinchillas in this study had significantly lower water intakes than the other two species, indicating particular species-specific adaptations to aridity. All chinchillas favoured open dishes, whereas the degus and guinea pigs had variable individual preferences. Water intake of chinchillas was similar or higher in this study than in previous studies where nipple drinkers were used. The results indicate that degus and guinea pigs can meet their drinking water needs with nipple drinkers; for chinchillas, other drinking systems may be more adequate.

Fecal cortisol levels predict breeding but not survival of females in the short-lived rodent, Octodon degus.

The cort-adaptation hypothesis indicates that an association between glucocorticoid (cort) levels and fitness may vary with the extent to which reproduction or breeding effort is a major determinant of cort levels. Support for a context dependent association between cort and fitness comes mostly from relatively long-lived, bird species. We tested the hypothesis that there are gender and context (life-history) specific cort-fitness relationships in degus, a short-lived and generally semelparous social rodent. In particular, we used demographical records on a natural population to estimate adult survival through seasons and years and linked that to records of baseline cort (based on fecal cortisol metabolites). We found no evidence for a direct relationship between baseline cort and adult survival across seasons, and this lack of association was recorded irrespective of sex and life history stage. Yet, cort levels during early lactation predicted the probability that females produce a second litter during the same breeding season, supporting a connection between baseline cort levels and breeding effort. Overall, the differential effects of cort on survival and breeding supported that the extent of cort-fitness relationships depends on the fitness component examined.

Habitat type influences endocrine stress response in the degu (Octodon degus).

While many studies have examined whether the stress response differs between habitats, few studies have examined this within a single population. This study tested whether habitat differences, both within-populations and between-populations, relate to differences in the endocrine stress response in wild, free-living degus (Octodon degus). Baseline cortisol (CORT), stress-induced CORT, and negative feedback efficacy were measured in male and female degus from two sites and three habitats within one site during the mating/early gestation period. Higher quality cover and lower ectoparasite loads were associated with lower baseline CORT concentrations. In contrast, higher stress-induced CORT but stronger negative feedback efficacy were associated with areas containing higher quality forage. Stress-induced CORT and body mass were positively correlated in female but not male degus across all habitats. Female degus had significantly higher stress-induced CORT levels compared to males. Baseline CORT was not correlated with temperature at time of capture and only weakly correlated with rainfall. Results suggest that degus in habitats with good cover quality, low ectoparasite loads, and increased food availability have decreased endocrine stress responses.

Recent rodent models for Alzheimer's disease: clinical implications and basic research.

Alzheimer's disease (AD) is the most common origin of dementia in the elderly. Although the cause of AD remains unknown, several factors have been identified that appear to play a critical role in the development of this debilitating disorder. In particular, amyloid precursor protein (APP), tau hyperphosphorylation, and the secretase enzymes, have become the focal point of recent research. Over the last two decades, several transgenic and non-transgenic animal models have been developed to elucidate the mechanistic aspects of AD and to validate potential therapeutic targets. Transgenic rodent models over-expressing human ß-amyloid precursor protein (ß-APP) and mutant forms of tau have become precious tools to study and understand the pathogenesis of AD at the molecular, cellular and behavioural levels, and to test new therapeutic agents. Nevertheless, none of the transgenic models of AD recapitulate fully all of the pathological features of the disease. Octodon degu, a South American rodent has been recently found to spontaneously develop neuropathological signs of AD in old age. This review aims to address the limitations and clinical relevance of transgenic rodent models in AD, and to highlight the potential for O. degu as a natural model for the study of AD neuropathology.

Characterization of the estrous cycle in Octodon degus.

We characterized the reproductive cycle of Octodon degus to determine whether reproductive maturation is spontaneous in juveniles and if ovarian cyclicity and luteal function are spontaneous in adults. Laboratory-reared prepubertal and adult females were monitored for vaginal patency and increased wheel-running. Sexual receptivity was assessed by pairing adult females with a male 1) continuously, 2) at the time of vaginal patency, or 3) following estradiol treatment. Blood samples were assayed for estradiol and progesterone concentrations on Days 1, 4, 8, and 16 relative to vaginal opening. Ovarian tissues were collected 6 and 16 days after behavioral estrus and 6 days after copulation for histology. In juveniles, the onset of cyclic vaginal patency and increased wheel-running activity was spontaneous, occurred in the absence of proximal male cues, and appeared at regular intervals (17.5 ± 1.4 days). In adults, vaginal patency and increased wheel-running occurred cyclically (21.2 ± 0.6 days) in the absence of proximal male cues, and these traits predicted the time of sexual receptivity. Corpora lutea develop spontaneously and are maintained for 12-14 days. The ovaries had well-developed corpora lutea 6 days after mating and 6 days after estrus without mating. Progesterone concentrations were highest in the second half of the cycle when corpora lutea were present and estradiol concentrations peaked on the day of estrus. Thus, female degus appear to exhibit a spontaneous reproductive cycle consistent with other Hystricognathi rodents. Octodon degus is a novel model with which to examine the mechanisms underlying different reproductive cycles.

Bottom-up control of consumers leads to top-down indirect facilitation of invasive annual herbs in semiarid Chile.

The abundance of exotic plants is thought to be limited by competition with resident species (including plants and generalist herbivores). In contrast, observations in semiarid Chile suggest that a native generalist rodent, the degu (Octodon degus), may be facilitating the expansion of exotic annual plants. We tested this hypothesis with a 20-year data set from a World Biosphere Reserve in mediterranean Chile. In this semiarid environment, rainfall varies annually and dramatically influences cover by both native and exotic annual plants; degu population density affects the composition and cover of exotic and native annual plants. In low-rainfall years, cover of both native and exotic herbs is extremely low. Higher levels of precipitation result in proportional increases in cover of all annual plants (exotic and native species), leading in turn to increases in degu population densities, at which point they impact native herbs in proportion to their greater cover, indirectly favoring the expansion of exotic plants. We propose that bottom-up control of consumers at our site results in top-down indirect facilitation of invasive annual herbs, and that this pattern may be general to other semiarid ecosystems.